HMGA2 is a specific immunohistochemical marker for pleomorphic adenoma and carcinoma ex‐pleomorphic adenoma

• DOI: 10.1111/his.13246
• Publication Date: 2017-05-02T15:02:13Z
• Authors: Jeffrey K Mito; Vickie Y Jo; Simion I Chiosea; Paola Dal Cin; Jeffrey F Krane
• Keywords: 0301 basic medicine; 03 medical and health sciences; HMGA2 Protein; Adenoma, Pleomorphic; Biomarkers, Tumor; Humans; Salivary Gland Neoplasms; Immunohistochemistry; In Situ Hybridization, Fluorescence; Salivary Glands; Translocation, Genetic

AimsAccurate classification of salivary gland neoplasms may be challenging, owing to morphological overlap, particularly in small biopsies. Recurrent translocations involving the high‐mobility group AT‐hook 2 (HMGA2) gene are present in a subset of pleomorphic adenomas (PAs) and carcinoma ex‐pleomorphic adenomas (CA ex‐PAs). The aim of this study was to evaluate immunohistochemical HMGA2 expression in 225 salivary gland tumours, including 56 PAs, 37 CA ex‐PAs, and 132 potential histological mimics, to determine its diagnostic utility.Methods and resultsHMGA2 expression was identified in 19 PAs (33.9%) and nine CA ex‐PAs (24.3%). Expression was strong and diffuse throughout all PAs, and in four of nine positive CA ex‐PAs. In five CA ex‐PAs, HMGA2 showed weak‐to‐strong multifocal staining within the carcinomatous component, and strong diffuse HMGA2 expression in the residual PA. Among histological mimics, six de‐novo salivary duct carcinomas (28.5%), three epithelial–myoepithelial carcinomas (33.3%) and one case each of myoepithelioma and basal cell adenoma expressed HMGA2. Fluorescence in‐situ hybridization for HMGA2 rearrangement performed on a subset of tumours that showed diffuse HMGA2 expression in PAs and CA ex‐PAs was frequently associated with rearrangement of the HMGA2 locus, whereas cases of de‐novo salivary duct carcinoma, or CA ex‐PA with limited or no HMGA2 expression, had an intact HMGA2 locus.ConclusionsHMGA2 expression is a highly specific (96.2%), but low‐sensitivity (29.8%), marker for PA and CA ex‐PA when compared with histological mimics, and is frequently associated with rearrangement of the HMGA2 locus.